1. Field of the Invention
The present invention relates to a liver regeneration accelerator which is capable of causing an increase in hepatic cells to regenerate the liver.
2. Discussion of the Background
Fulminant hepatitis is the description of a condition involving sudden, widespread necrosis of hepatic cells due to causes such as the hepatitis virus, etc. Treatment of fulminant hepatitis includes interferon therapy, conventional anti-virus therapy, and the use of medicines which are generally used in the treatment of hepatitis. However, no direct effect on liver regeneration has been observed for interferon, while Glutathione and Tathion (Yamanouchi Seiyaku Co.) and Stronger Neo-Minophagen C (Minophagen Co.), which are generally used for hepatitis, improve the plasma transaminase value, but their effect on liver regeneration is limited.
Known therapeutic agents for liver damage serve to improve the function of liver tissue which has survived the initial cause of damage, however, the present goal is not simply to improve the condition of damaged tissue, but regeneration of liver cells by growth factors specific to hepatocytes. A known example of such an agent is hepatocyte growth factor (HGF), which stimulates the proliferation of cultured hepatocytes, and has an effect during cell division of hepatocytes, particularly during the G1 phase (DNA synthesis preinterphase) of the cell cycle. It is recognized as the major factor causing migration of hepatocytes to the S phase (DNA synthesis phase). This factor was expected to induce liver regeneration in the clinic as well. However, no improvement in the condition of patients with acute liver failure was observed despite high concentrations of HGF in the peripheral blood. Thus an awareness is growing of the necessity of participation of a factor other than HGF for liver regeneration, but so far no such factor capable of inducing liver regeneration in vivo to any significant degree has been discovered.
Masaki et al (U.S. Pat. No. 4,987,123) teaches that a composition comprising L-alanine and L-glutamine promotes ethanol clearance from blood and suppresses the serum enzymatic activities of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and ornithine carbamyl transferase (OCT) which are symptoms associated with alcoholic hepatitis. It was found that alanine and glutamine could help restore liver function after ethanol loading.
Suda et al U.S. Pat. No. 4,596,825 teach a pharmaceutical composition for preventing or alleviating the effects of acute alcoholism, in particular liver disturbances in mammals, which comprises a mixture of alanine and ornithine. These compounds accelerate removal of ethanol and increase blood sugar and have a life saving affect in tests involving acute ethanol intoxication. Alleviation of disturbances in liver tissue was also noted.
The methods discussed above are known to reduce the incidence of swollen liver cells and improve the overall function of remaining liver tissue. However, no factor capable of inducing liver regeneration was described.
The present invention aims to provide an effective liver regeneration accelerator which is capable of causing an increase in hepatic cells to accelerate liver regeneration after liver tissue has been destroyed by disease or surgical procedures. In addition, the present invention is useful in liver transplantation procedures.